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NOT Open Access | Metabolic survival adaptations of Plasmodium falciparum exposed to sub-lethal doses of fosmidomycin

January 27, 2021 - 10:29 -- NOT Open Access
Tewari SG, Rajaram K, Swift RP, Reifman J, Prigge ST, Wallqvist A
Antimicrob Agents Chemother. 2021 Jan 25:AAC.02392-20

The malaria parasite Plasmodium falciparum contains the apicoplast organelle that synthesize isoprenoids, which are metabolites necessary for post-translational modification of Plasmodium proteins. We used fosmidomycin, an antibiotic that inhibits isoprenoid biosynthesis, to identify mechanisms that underlie the development of the parasite's adaptation to the drug at sub-lethal concentrations. We first determined a concentration of fosmidomycin that reduced parasite growth by ∼50% over one intraerythrocytic developmental cycle (IDC). At this dose, we maintained synchronous parasite cultures for one full IDC, and collected metabolomic and transcriptomic data at multiple time points to capture global and stage-specific alterations.

NOT Open Access | Plasmodium infection and drug cure for malaria vaccine development

January 13, 2021 - 11:15 -- NOT Open Access
Nevagi RJ, Good MF, Stanisic DI
Expert Rev Vaccines. 2021 Jan 11

Despite decades of research into the development of a vaccine to combat the malaria parasite, a highly efficacious malaria vaccine is not yet available. Different whole parasite-based vaccine approaches, including deliberate Plasmodium infection and drug cure (IDC), have been evaluated in pre-clinical and early phase clinical trials.

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